Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) is the most common breast cancer, making up more than 70% of all cases. Although HR+/HER2- breast cancer often has better outcomes than other types, it still presents long-term challenges, because it can recur (come back) several years after treatment.
In fact, according to a recent study, up to 30% of people with early-stage HR+/HER2- breast cancer may experience recurrence. This can happen even up to 10 years after diagnosis. In some cases, those with HR+/HER2- breast cancer who have early recurrence may not notice any obvious symptoms, and routine checkups may not detect any new changes. Sometimes, the cancer is found after it has already spread (metastasized) to other areas of the body.
Today, researchers of the CATE clinical trial are asking the question, ‘What if we could detect this recurrence earlier and act on it before symptoms appear?’ By combining ctDNA monitoring with a targeted therapy called elacestrant, researchers are taking a proactive approach, aiming to detect early signs of recurrence and intervene before the cancer has a chance to come back.
Accelerating Early Breast Cancer Detection with ctDNA
Circulating tumor DNA (ctDNA) is an emerging and promising tool that may provide doctors with a new way to track cancer and help them identify more tailored treatments for each patient. Through a simple blood test, also known as liquid biopsy, doctors can obtain important information about a patient’s cancer. For those who are at a higher risk of recurrence, this “window” of insight may help doctors detect metastasis even earlier and create a plan.
“There is increasing data coming out that ctDNA is a sensitive and specific predictor of metastatic recurrence and that there is a lag time of around 12 months between a positive ctDNA test and finding a metastatic recurrence on scans,” explains Mariya Rozenblit, M.D. “This provides a window in which to see if early treatment can potentially clear ctDNA and prevent clinical metastatic recurrence.”
Dr. Rozenblit is a medical oncologist at Yale University and principal investigator of the CATE clinical trial. The CATE trial not only offers participants the possibility of improved disease surveillance through ctDNA testing but also access to a more targeted and personalized treatment for HR+/HER2- breast cancer.
Unlocking the Promise of Elacestrant
The phase 2, multicenter CATE trial is sponsored by the Translational Breast Cancer Research Consortium (TBCRC) which is funded in part by Susan G. Komen®, and also funded by Stemline Therapeutics and Personalis. This study is investigating whether elacestrant, a selective estrogen receptor degrader (SERD), can benefit people with HR+/HER2- breast cancer who have the highest risk of recurrence, as identified by a liquid biopsy. CATE is also a single-arm study, meaning that all participants receive the new treatment and there is no control group that gets the current standard of care.
If a participant’s blood tests positive for ctDNA, they will immediately begin treatment with elacestrant. Elacestrant has already shown promise in recent clinical trials as a more tolerable and effective treatment for people living with metastatic breast cancer (MBC). Unlike older hormone therapies that only block estrogen from reaching the cell’s receptor, elacestrant breaks down and destroys the estrogen receptor completely. As an oral tablet, it is also more appealing to patients than a monthly injection.
“Elacestrant is a great choice because it’s oral and very well tolerated,” Dr. Rozenblit explains. “It is known to be more effective than fulvestrant in the metastatic setting, and therefore, we predict it will be more effective than aromatase inhibitors or tamoxifen.”
Once they begin treatment, participants will continue to have their ctDNA levels tested every three months, and then every six months during their follow-up. Researchers will continually check for ctDNA clearance, or whether the treatment has successfully made the tumor’s DNA in the blood disappear. Dr. Rozenblit and her team hope that this comprehensive strategy will also bring improvements in long-term outcomes and survival for these patients.
“We are investigating ctDNA clearance in this trial, but also recurrence-free survival,” Dr. Rozenblit says. “Ultimately, we want to see that early intervention leads to reducing risk of metastatic recurrence.”
A Chance to Rewrite the Future
For people living with HR+/HER2- breast cancer, the risk of recurrence hovers over them like a shadow, with a feeling of uncertainty that lasts for many years. With promising results from the CATE clinical trial, patients may have the opportunity to face that uncertainty head on. They can be proactive in their care rather than reactive and always waiting for the other shoe to drop.
With the successful innovation of ctDNA monitoring and treatment with elacestrant, people with HR+/HER2- breast cancer, especially those with a high risk of recurrence, could have the power to change the trajectory of their treatment and rewrite the future of their care. While ctDNA testing is under study and currently available for some people with early-stage breast cancer at some places, it is not currently in clinical care guidelines. For now, more clinical trials like CATE are needed to demonstrate the potential benefits that ctDNA testing could bring these patients.
“The biggest barrier is that we need evidence that proactive care works,” Dr. Rozenblit says. “Right now, ctDNA testing remains expensive and we very much need more funding to support randomized trials to establish the clinical utility of ctDNA-guided therapy.”
Learn more about the CATE clinical trial.
Explore the trial fact sheet: Spotlight on Clinical Trials_TBCRC-068_vs2.pdf
